Pharmacokinetic interaction of ibuprofen enantiomers in rabbits |
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Authors: | Lin Wenhui Hayakawa Toru Yanaguimoto Hitomi Kuzuba Mamoru Obara Takako Ding Guohua Cui Fude Inotsume Nobuo |
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Affiliation: | Department of Pharmacology and Therapeutics, Hokkaido College of Pharmacy, Katsuraoka, Otaru 047-0264, Japan. |
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Abstract: | The potential interaction between two ibuprofen enantiomers was studied after intravenous administration of R-(-)-, S-(+)- and racemic ibuprofen to rabbits. The total body clearance values calculated by compartmental model analysis (0.65 +/- 0.21 for R-(-)-ibuprofen and 0.63 +/- 0.34 for S-(+)-ibuprofen) after intravenous administration of the racemate of ibuprofen were significantly smaller than those of individual enantiomers (0.95 +/- 0.23 for R-(-)-ibuprofen and 1.03 +/- 0.23 for S-(+)-ibuprofen), indicating that the enantiomer-enantiomer interaction results in a mutual inhibition. The enantiomeric interaction in the pharmacokinetic behaviour of ibuprofen after racemic administration is considered to be a result of an alteration in the metabolic or excretion phase (or both) rather than stereoselective protein binding in the systemic distribution. |
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